Tissue engineering holds great promise to enable alternative therapies for diseases such as diabetes, kidney, liver, and heart failure. A common approach in tissue engineering is seeding cells in biodegradable scaffolds (top-down), which brings cells together to mimic native tissues. These scaffolds are expected to degrade and be replaced by cellular growth and extracellular matrix deposition over time. Challenges in current tissue engineering approaches are: (i) achieving complex three-dimensional (3D) cellular architecture and organization, (ii) control over cellular proximity and microscale resolution, (iii) enhancing transport through scaffold porosity and embedded microchannels, mimicking vascular network in vivo. Directed assembly of nano- and micro-scale particles is of great interest and has found applications in many fields including electronics, nanomaterials, and holds great potential for tissue engineering. Tissues are made up of repeating functional units. Bottom-up tissue engineering aims to assemble microscale hydrogels (microgels) as building blocks to form organized 3D tissue constructs with spatial control over microarchitecture mimicking native tissues. The intellectual merit of this proposal lies in developing a platform technology that utilizes nanoparticles and microgels as building blocks to create 3D complex multi-layer constructs via external magnetic fields. The final outcome of the project will offer a broadly applicable, nanoparticle-based, "magnetic-induced microgel assembly" platform. This platform would become a broadly available biotechnological tool and method to create 3D tissue models in vitro that could be used for tissue/organ replacement, regenerative medicine, high throughput screening, as well as pharmaceutical drug discovery. The outcomes of this project will open new avenues for physical and biologic research and have a considerable impact on fundamental and applied science, education, and medicine. The broader impacts of this proposal include educational aims to involve, train and mentor: a) local Boston high school students from the lowest income communities through Brigham and Women's Hospital Student Success Jobs Program, b) undergraduate students through Massachusetts Institute of Technology Undergraduate Research Opportunities Program, and c) graduate students to translate book-based knowhow to practice by utilizing the principles identified in this project on the complex multidisciplinary nature of magnetic assembly of microscale structures. The broader impacts of the proposed research cover levels at the local, national and international education with an extended influence on public awareness about the interface of biology and microfluidic technologies. At the local level, the aim is to provide students with experience with interdisciplinary science, allowing them to perform research and learn scientific methods. Further, the principal investigator (PI) will recruit students from Harvard University's underrepresented minority research program. This program brings underrepresented minorities and women to Harvard from other universities every summer allowing them to work on the proposed research project. The PI will also develop graduate courses and arrange field trips with local high schools in educating students about microfluidics research. At the national level, the PI will educate the students and the public at other institutions on technological and scientific challenges. Additionally, the PI will pursue international educational efforts as well as play a role as a lecturer for activities such as NSF supported international summer schools.

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Stanford University
United States
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